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  • 1.

    【2hr】Species Identity Supersedes the Dilution Effect Concerning Hantavirus Prevalence at Sites across Texas and México

    包量

    机译 物种身份取代了德克萨斯州和墨西哥各地有关汉坦病毒流行的稀释效应
    摘要：Recent models suggest a relationship exists between community diversity and pathogen prevalence, the proportion of individuals in a population that are infected by a pathogen, with most inferences tied to assemblage structure. Two contrasting outcomes of this relationship have been proposed: the “dilution effect” and the “amplification effect.” Small mammal assemblage structure in disturbed habitats often differs from assemblages in sylvan environments, and hantavirus prevalence is often negatively correlated with habitats containing high species diversity via dilution effect dynamics. As species richness increases, prevalence of infection often is decreased. However, anthropogenic changes to sylvan landscapes have been shown to decrease species richness and/or increase phylogenetic similarities within assemblages. Between January 2011 and January 2016, we captured and tested 2406 individual small mammals for hantavirus antibodies at 20 sites across Texas and México and compared differences in hantavirus seroprevalence, species composition, and assemblage structure between sylvan and disturbed habitats. We found 313 small mammals positive for antibodies against hantaviruses, evincing an overall prevalence of 9.7% across all sites. In total, 40 species of small mammals were identified comprising 2 taxonomic orders (Rodentia and Eulipotyphla). By sampling both habitat types concurrently, we were able to make real-world inferences into the efficacy of dilution effect theory in terms of hantavirus ecology. Our hypothesis predicting greater species richness higher in sylvan habitats compared to disturbed areas was not supported, suggesting the characteristics of assemblage structure do not adhere to current conceptions of species richness negatively influencing prevalence via a dilution effect.
  • 2.

    【2hr】Nonhuman Primate Models and Understanding the Pathogenesis of HIV Infection and AIDS

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    机译 非人类灵长类动物模型和艾滋病毒感染和艾滋病的发病机理的了解
    摘要：Research using nonhuman primates (NHPs) as models for human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) has resulted in tremendous achievements not only in the prevention and treatment of HIV, but also in biomedical research more broadly. Once considered a death sentence, HIV infection is now fairly well controlled with combination antiretroviral treatments, almost all of which were first tested for efficacy and safety in nonhuman primates or other laboratory animals. Research in NHP has led to “dogma changing” discoveries in immunology, infectious disease, and even our own genetics. We now know that many of our genes are retroviral remnants, or developed in response to archaic HIV-like retroviral infections. Early studies involving blood from HIV patients and in experiments in cultured tissues contributed to confusion regarding the cause of AIDS and impeded progress in the development of effective interventions. Research on the many retroviruses of different NHP species have broadened our understanding of human immunology and perhaps even our origins and evolution as a species. In combination with recent advances in molecular biology and computational analytics, research in NHPs has unique potential for discoveries that will directly lead to new cures for old human and animal diseases, including HIV/AIDS.
  • 3.

    【2hr】The Chimpanzee Model of Viral Hepatitis: Advances in Understanding the Immune Response and Treatment of Viral Hepatitis

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    机译 病毒性肝炎的黑猩猩模型：了解免疫反应和治疗病毒性肝炎的进展
    摘要：Chimpanzees (Pan troglodytes) have contributed to diverse fields of biomedical research due to their close genetic relationship to humans and in many instances due to the lack of any other animal model. This review focuses on the contributions of the chimpanzee model to research on hepatitis viruses where chimpanzees represented the only animal model (hepatitis B and C) or the most appropriate animal model (hepatitis A). Research with chimpanzees led to the development of vaccines for HAV and HBV that are used worldwide to protect hundreds of millions from these diseases and, where fully implemented, have provided immunity for entire generations. More recently, chimpanzee research was instrumental in the development of curative therapies for hepatitis C virus infections. Over a span of 40 years, this research would identify the causative agent of NonA,NonB hepatitis, validate the molecular tools for drug discovery, and provide safety and efficacy data on the therapies that now provide a rapid and complete cure of HCV chronic infections. Several cocktails of antivirals are FDA approved that eliminate the virus following 12 weeks of once-per-day oral therapy. This represents the first cure of a chronic viral disease and, once broadly implemented, will dramatically reduce the occurrence of cirrhosis and liver cancer. The recent contributions of chimpanzees to our current understanding of T cell immunity for HCV, development of novel therapeutics for HBV, and the biology of HAV are reviewed. Finally, a perspective is provided on the events leading to the cessation of the use of chimpanzees in research and the future of the chimpanzees previously used to bring about these amazing breakthroughs in human healthcare.
  • 4.

    【2hr】Nonhuman Primates: A Vital Model for Basic and Applied Research on Female Reproduction Prenatal Development and Womens Health

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    机译 非人类灵长类动物：关于女性生殖产前发育和妇女健康的基础和应用研究的重要模型
    摘要：The comparative biology of reproduction and development in mammalian species is remarkable. Hence, because of similarities in environmental and neuroendocrine control of the reproductive axis, the cyclic function of the ovary and reproductive tract, establishment and control of the maternal-fetal-placental unit during pregnancy, and reproductive aging from puberty through menopause, nonhuman primates (NHPs) are valuable models for research related to women's reproductive health and its disorders. This chapter provides examples of research over the past 10+ years using Old World monkeys (notably macaque species), baboons, and to a lesser extent New World monkeys (especially marmosets) that contributed to our understanding of the etiology and therapies or prevention of: (1) ovarian disorders, e.g., polycystic ovary syndrome, mitochondrial DNA-based diseases from the oocyte; (2) uterine disorders, for example, endometriosis and uterine transplantation; and (3) pregnancy disorders, for example, preterm labor and delivery, environmental factors. Also, emerging opportunities such as viral (e.g., Zika) induced fetal defects and germline genomic editing to generate valuable primate models of human diseases (e.g., Huntington and muscular dystrophy) are addressed. Although the high costs, specialized resources, and ethical debate challenge the use of primates in biomedical research, their inclusion in fertility and infertility research is vital for continued improvements in women's reproductive health.
  • 5.

    【2hr】Rat Genome and Model Resources

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    机译 大鼠基因组和模型资源
    摘要：Rats remain a major model for studying disease mechanisms and discovery, validation, and testing of new compounds to improve human health. The rat’s value continues to grow as indicated by the more than 1.4 million publications (second to human) at PubMed documenting important discoveries using this model. Advanced sequencing technologies, genome modification techniques, and the development of embryonic stem cell protocols ensure the rat remains an important mammalian model for disease studies. The 2004 release of the reference genome has been followed by the production of complete genomes for more than two dozen individual strains utilizing NextGen sequencing technologies; their analyses have identified over 80 million variants. This explosion in genomic data has been accompanied by the ability to selectively edit the rat genome, leading to hundreds of new strains through multiple technologies. A number of resources have been developed to provide investigators with access to precision rat models, comprehensive datasets, and sophisticated software tools necessary for their research. Those profiled here include the Rat Genome Database, PhenoGen, Gene Editing Rat Resource Center, Rat Resource and Research Center, and the National BioResource Project for the Rat in Japan.
  • 6.

    【2hr】Zebrafish Models of Human Disease: Gaining Insight into Human Disease at ZFIN

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    机译 斑马鱼人类疾病模型：在ZFIN上深入了解人类疾病
    摘要：The Zebrafish Model Organism Database (ZFIN; https://zfin.org) is the central resource for genetic, genomic, and phenotypic data for zebrafish (Danio rerio) research. ZFIN continuously assesses trends in zebrafish research, adding new data types and providing data repositories and tools that members of the research community can use to navigate data. The many research advantages and flexibility of manipulation of zebrafish have made them an increasingly attractive animal to model and study human disease.To facilitate disease-related research, ZFIN developed support to provide human disease information as well as annotation of zebrafish models of human disease. Human disease term pages at ZFIN provide information about disease names, synonyms, and references to other databases as well as a list of publications reporting studies of human diseases in which zebrafish were used. Zebrafish orthologs of human genes that are implicated in human disease etiology are routinely studied to provide an understanding of the molecular basis of disease. Therefore, a list of human genes involved in the disease with their corresponding zebrafish ortholog is displayed on the disease page, with links to additional information regarding the genes and existing mutations. Studying human disease often requires the use of models that recapitulate some or all of the pathologies observed in human diseases. Access to information regarding existing and published models can be critical, because they provide a tractable way to gain insight into the phenotypic outcomes of the disease. ZFIN annotates zebrafish models of human disease and supports retrieval of these published models by listing zebrafish models on the disease term page as well as by providing search interfaces and data download files to access the data. The improvements ZFIN has made to annotate, display, and search data related to human disease, especially zebrafish models for disease and disease-associated gene information, should be helpful to researchers and clinicians considering the use of zebrafish to study human disease.
  • 7.

    【2hr】Informatics Support for Basic Research in Biomedicine

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    机译 信息学对生物医学基础研究的支持
    摘要：Informatics methodologies exploit computer-assisted techniques to help biomedical researchers manage large amounts of information. In this paper, we focus on the biomedical research literature (MEDLINE). We first provide an overview of some text mining techniques that offer assistance in research by identifying biomedical entities (e.g., genes, substances, and diseases) and relations between them in text.We then discuss Semantic MEDLINE, an application that integrates PubMed document retrieval, concept and relation identification, and visualization, thus enabling a user to explore concepts and relations from within a set of retrieved citations. Semantic MEDLINE provides a roadmap through content and helps users discern patterns in large numbers of retrieved citations. We illustrate its use with an informatics method we call “discovery browsing,” which provides a principled way of navigating through selected aspects of some biomedical research area. The method supports an iterative process that accommodates learning and hypothesis formation in which a user is provided with high level connections before delving into details.As a use case, we examine current developments in basic research on mechanisms of Alzheimer’s disease. Out of the nearly 90 000 citations returned by the PubMed query “Alzheimer’s disease,” discovery browsing led us to 73 citations on sortilin and that disorder. We provide a synopsis of the basic research reported in 15 of these. There is wide-spread consensus among researchers working with a range of animal models and human cells that increased sortilin expression and decreased receptor expression are associated with amyloid beta and/or amyloid precursor protein.
  • 8.

    【2hr】Accelerating Biomedical Discoveries through Rigor and Transparency

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    机译 通过严格和透明化加速生物医学发现
    摘要：Difficulties in reproducing published research findings have garnered a lot of press in recent years. As a funder of biomedical research, the National Institutes of Health (NIH) has taken measures to address underlying causes of low reproducibility. Extensive deliberations resulted in a policy, released in 2015, to enhance reproducibility through rigor and transparency. We briefly explain what led to the policy, describe its elements, provide examples and resources for the biomedical research community, and discuss the potential impact of the policy on translatability with a focus on research using animal models. Importantly, while increased attention to rigor and transparency may lead to an increase in the number of laboratory animals used in the near term, it will lead to more efficient and productive use of such resources in the long run. The translational value of animal studies will be improved through more rigorous assessment of experimental variables and data, leading to better assessments of the translational potential of animal models, for the benefit of the research community and society.
  • 9.

    【2hr】Nonhuman Primate Studies to Advance Vision Science and Prevent Blindness

    包量

    机译 非人类灵长类动物研究以促进视觉科学和预防失明
    摘要：Most primate behavior is dependent on high acuity vision. Optimal visual performance in primates depends heavily upon frontally placed eyes, retinal specializations, and binocular vision. To see an object clearly its image must be placed on or near the fovea of each eye. The oculomotor system is responsible for maintaining precise eye alignment during fixation and generating eye movements to track moving targets. The visual system of nonhuman primates has a similar anatomical organization and functional capability to that of humans. This allows results obtained in nonhuman primates to be applied to humans. The visual and oculomotor systems of primates are immature at birth and sensitive to the quality of binocular visual and eye movement experience during the first months of life. Disruption of postnatal experience can lead to problems in eye alignment (strabismus), amblyopia, unsteady gaze (nystagmus), and defective eye movements. Recent studies in nonhuman primates have begun to discover the neural mechanisms associated with these conditions. In addition, genetic defects that target the retina can lead to blindness. A variety of approaches including gene therapy, stem cell treatment, neuroprosthetics, and optogenetics are currently being used to restore function associated with retinal diseases. Nonhuman primates often provide the best animal model for advancing fundamental knowledge and developing new treatments and cures for blinding diseases.
  • 10.

    【2hr】Naturally Occurring Nonhuman Primate Models of Psychosocial Processes

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    机译 社会过程的自然存在的非人类灵长类动物模型
    摘要：Human research into psychological processes such as anxiety, depression, or loneliness typically involves accruing cases in which the phenomenon of interest is naturally occurring, and then comparing such a sample with control cases. In contrast, animal research designed to model similar processes to test mechanistic hypotheses typically involves inducing the phenomenon of interest via some exogenously (i.e., human) administered procedure. In the present review, the author proposes that naturally occurring animal models can complement induced models in understanding complex psychological phenomena. Advantages and disadvantages of naturally occurring versus induced models are described, and detailed examples of three naturally occurring models—for loneliness and health, behavioral inhibition and asthma, and social functioning and autism—are described, along with a formal program (the BioBehavioral Assessment program) at the California National Primate Research Center, that is designed to quantify variation in biobehavioral processes in infant rhesus macaques to facilitate development of naturally occurring models. It is argued that, because of the similarity in complex behavioral and psychological processes between macaques and humans, naturally occurring primate models provide a bridge between human studies and induced primate models and have the potential to identify new models for translational research.
  • 11.

    【2hr】Environmental Enrichment in the 21st Century

    包量

    机译 21世纪的环境富裕
    摘要：More than a quarter of a century has elapsed since the Animal Welfare Act mandated that research facilities develop and follow a plan to promote the psychological well-being of captive primates. Since passage of this law, considerable effort and resources have been directed to designing environmental enrichment strategies in an effort to improve animal welfare. These plans typically consist of environmental enrichment and socialization efforts. While environmental enhancement has undergone a great deal of improvement in the past 25 years, it should be viewed as a continual work in progress, which takes advantage of emergent and future technologies. In this review, we discuss the objectives of the environmental enhancement plan along with relevant outcome measures, as well as ongoing challenges, costs, and benefits. We then review various enrichment strategies and assess their efficacy in meeting goals and objectives. Finally, we look forward to consider what the future might hold for environmental enrichment of nonhuman primates used in research.
  • 12.

    【2hr】Opportunities to Apply the 3Rs in Safety Assessment Programs

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    机译 在安全评估计划中应用3R的机会
    摘要：Before a potential new medicine can be administered to humans it is essential that its safety is adequately assessed. Safety assessment in animals forms an integral part of this process, from early drug discovery and initial candidate selection to the program of recommended regulatory tests in animals. The 3Rs (replacement, reduction, and refinement of animals in research) are integrated in the current regulatory requirements and expectations and, in the EU, provide a legal and ethical framework for in vivo research to ensure the scientific objectives are met whilst minimizing animal use and maintaining high animal welfare standards. Though the regulations are designed to uncover potential risks, they are intended to be flexible, so that the most appropriate approach can be taken for an individual product. This article outlines current and future opportunities to apply the 3Rs in safety assessment programs for pharmaceuticals, and the potential (scientific, financial, and ethical) benefits to the industry, across the drug discovery and development process. For example, improvements to, or the development of, novel, early screens (e.g., in vitro, in silico, or nonmammalian screens) designed to identify compounds with undesirable characteristics earlier in development have the potential to reduce late-stage attrition by improving the selection of compounds that require regulatory testing in animals. Opportunities also exist within the current regulatory framework to simultaneously reduce and/or refine animal use and improve scientific outcomes through improvements to technical procedures and/or adjustments to study designs. It is important that approaches to safety assessment are continuously reviewed and challenged to ensure they are science-driven and predictive of relevant effects in humans.
  • 13.

    【2hr】Mouse Models for Drug Discovery. Can New Tools and Technology Improve Translational Power?

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    机译 用于药物发现的鼠标模型。新工具和新技术能否提高翻译能力？
    摘要：The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology. These technological advances come at a time when cost reductions in genome sequencing have led to the identification of pathogenic mutations in patient populations, providing unprecedented opportunities in the use of mice to model human disease. The ease of genetic engineering in mice also offers a potential paradigm shift in resource sharing and the speed by which models are made available in the public domain. Predictively, the knowledge alone that a model can be quickly remade will provide relief to resources encumbered by licensing and Material Transfer Agreements. For decades, mouse strains have provided an exquisite experimental tool to study the pathophysiology of the disease and assess therapeutic options in a genetically defined system. However, a major limitation of the mouse has been the limited genetic diversity associated with common laboratory mice. This has been overcome with the recent development of the Collaborative Cross and Diversity Outbred mice. These strains provide new tools capable of replicating genetic diversity to that approaching the diversity found in human populations. The Collaborative Cross and Diversity Outbred strains thus provide a means to observe and characterize toxicity or efficacy of new therapeutic drugs for a given population. The combination of traditional and contemporary mouse genome editing tools, along with the addition of genetic diversity in new modeling systems, are synergistic and serve to make the mouse a better model for biomedical research, enhancing the potential for preclinical drug discovery and personalized medicine.
  • 14.

    【2hr】Lessons Learned from Mouse Mammary Tumor Virus in Animal Models

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    机译 在动物模型中从小鼠乳腺肿瘤病毒中学到的教训
    摘要：Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious, cancer-inducing agent in the 1930s, has been used as an animal model for the study of retroviral infection and transmission, antiviral immune responses, and breast cancer and lymphoma biology. The main target cells for MMTV infection in vivo are cells of the immune system and mammary epithelial cells. Although the host mounts an immune response to the virus, MMTV has evolved multiple means of evading this response. MMTV causes mammary tumors when the provirus integrates into the mammary epithelial and lymphoid cell genome during viral replication and thereby activates cellular oncogene expression. Thus, tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer.
  • 15.

    【2hr】Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model

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    机译 新西兰白兔肠道相关淋巴组织的表征和用作病毒肿瘤学动物模型
    摘要：Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route.
  • 16.

    【2hr】Murine Tumor Models for Oncolytic Rhabdo-Virotherapy

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    机译 溶瘤性弹道病毒疗法的鼠肿瘤模型
    摘要：The preclinical optimization and validation of novel treatments for cancer therapy requires the use of laboratory animals. Although in vitro experiments using tumor cell lines and ex vivo treatment of patient tumor samples provide a remarkable first-line tool for the initial study of tumoricidal potential, tumor-bearing animals remain the primary option to study delivery, efficacy, and safety of therapies in the context of a complete tumor microenvironment and functional immune system. In this review, we will describe the use of murine tumor models for oncolytic virotherapy using vesicular stomatitis virus. We will discuss studies using immunocompetent and immunodeficient models with respect to toxicity and therapeutic treatments, as well as the various techniques and tools available to study cancer therapy with Rhabdoviruses.
  • 17.

    【2hr】The Altered Schaedler Flora: Continued Applications of a Defined Murine Microbial Community

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    机译 改变的舍德勒植物群：定义的小鼠微生物群落的继续应用
    摘要：The gastrointestinal (GI) microbiota forms a mutualistic relationship with the host through complex and dynamic interactions. Because of the complexity and interindividual variation of the GI microbiota, investigating how members of the microbiota interact with each other, as well as with the host, is daunting. The altered Schaedler flora (ASF) is a model community of eight microorganisms that was developed by R.P. Orcutt and has been in use since the late 1970s. The eight microorganisms composing the ASF were all derived from mice, can be cultured in vitro, and are stably passed through multiple generations (at least 15 years or more by the authors) in gnotobiotic mice continually bred in isolator facilities. With the limitations associated with conventional, mono- or biassociated, and germfree mice, use of mice colonized with a consortium of known bacteria that naturally inhabit the murine gut offers a powerful system to investigate mechanisms governing host–microbiota relationships, and how members of the GI microbiota interact with one another. The ASF community offers significant advantages to study homeostatic as well as disease-related interactions by taking advantage of a well-defined, limited community of microorganisms. For example, quantification and spatial distribution of individual members, microbial genetic manipulation, genomic-scale analysis, and identification of microorganism-specific host immune responses are all achievable using the ASF model. This review compiles highlights associated with the 37-year history of the ASF, including descriptions of its continued use in biomedical research to elucidate the complexities of host-microbiome interactions in health and disease.
  • 18.

    【2hr】Porcine Models of Muscular Dystrophy

    包量

    机译 肌营养不良症的猪模型
    摘要：Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein dystrophin. This disease has been studied using a variety of animal models including fish, mice, rats, and dogs. While these models have contributed substantially to our mechanistic understanding of the disease and disease progression, limitations inherent to each model have slowed the clinical advancement of therapies, which necessitates the development of novel large-animal models. Several porcine dystrophin-deficient models have been identified, although disease severity may be so severe as to limit their potential contributions to the field. We have recently identified and completed the initial characterization of a natural porcine model of dystrophin insufficiency. Muscles from these animals display characteristic focal necrosis concomitant with decreased abundance and localization of dystrophin-glycoprotein complex components. These pigs recapitulate many of the cardinal features of muscular dystrophy, have elevated serum creatine kinase activity, and preliminarily appear to display altered locomotion. They also suffer from sudden death preceded by EKG abnormalities. Pig dystrophinopathy models could allow refinement of dosing strategies in human-sized animals in preparation for clinical trials. From an animal handling perspective, these pigs can generally be treated normally, with the understanding that acute stress can lead to sudden death. In summary, the ability to create genetically modified pig models and the serendipitous discovery of genetic disease in the swine industry has resulted in the emergence of new animal tools to facilitate the critical objective of improving the quality and length of life for boys afflicted with such a devastating disease.
  • 19.

    【2hr】Beyond the Mouse Monopoly: Studying the Male Germ Line in Domestic Animal Models

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    机译 超越老鼠的垄断：在家畜模型中研究雄性生殖系
    摘要：Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis and essential to maintain the continuous production of spermatozoa after the onset of puberty in the male. The study of the male germ line is important for understanding the process of spermatogenesis, unravelling mechanisms of stemness maintenance, cell differentiation, and cell-to-cell interactions. The transplantation of SSCs can contribute to the preservation of the genome of valuable individuals in assisted reproduction programs. In addition to the importance of SSCs for male fertility, their study has recently stimulated interest in the generation of genetically modified animals because manipulations of the male germ line at the SSC stage will be maintained in the long term and transmitted to the offspring. Studies performed mainly in the mouse model have laid the groundwork for facilitating advancements in the field of male germ line biology, but more progress is needed in nonrodent species in order to translate the technology to the agricultural and biomedical fields. The lack of reliable markers for isolating germ cells from testicular somatic cells and the lack of knowledge of the requirements for germ cell maintenance have precluded their long-term maintenance in domestic animals. Nevertheless, some progress has been made. In this review, we will focus on the state of the art in the isolation, characterization, culture, and manipulation of SSCs and the use of germ cell transplantation in domestic animals.
  • 20.

    【2hr】The Significance of Meaning: Why Do Over 90 of BehavioralNeuroscience Results Fail to Translate to Humans and What Can We Do to FixIt?

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    机译 意义的意义：为什么超过90％的行为神经科学结果无法翻译成人类我们该怎么办它？
    摘要：The vast majority of drugs entering human trials fail. This problem (called “attrition”) is widely recognized as a public health crisis, and has been discussed openly for the last two decades. Multiple recent reviews argue that animals may be just too different physiologically, anatomically, and psychologically from humans to be able to predict human outcomes, essentially questioning the justification of basic biomedical research in animals.This review argues instead that the philosophy and practice of experimental design and analysis is so different in basic animal work and human clinical trials that an animal experiment (as currently conducted) cannot reasonably predict the outcome of a human trial. Thus, attrition does reflect a lack of predictive validity of animal experiments, but it would be a tragic mistake to conclude that animal models cannot show predictive validity.A variety of contributing factors to poor validity are reviewed. The need to adopt methods and models that are highly specific (i.e., which can identify true negative results) in order to complement the current preponderance of highly sensitive methods (which are prone to false positive results) is emphasized. Concepts in biomarker-based medicine are offered as a potential solution, and changes in the use of animal models required to embrace a translational biomarker-based approach are outlined. In essence, this review advocates a fundamental shift, where we treat everyaspect of an animal experiment that we can as if it was a clinical trial in a humanpopulation.However, it is unrealistic to expect researchers to adopt a new methodology thatcannot be empirically justified until a successful human trial. “Validationwith known failures” is proposed as a solution. Thus new methods or models canbe compared against existing ones using a drug that has translated (a known positive)and one that has failed (a known negative). Current methods should incorrectlyidentify both as effective, but a more specific method should identify the negativecompound correctly. By using a library of known failures we can thereby empiricallytest the impact of suggested solutions such as enrichment, controlledheterogenization, biomarker-based models, or reverse-translated measures.
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